U.S. patent application number 12/990179 was filed with the patent office on 2011-05-05 for method for selecting bolus doses and bolus delivery patterns in a drug delivery device.
Invention is credited to Iddo Gescheit, Gali Shapira, Ofer Yodfat.
Application Number | 20110106050 12/990179 |
Document ID | / |
Family ID | 41255505 |
Filed Date | 2011-05-05 |
United States Patent
Application |
20110106050 |
Kind Code |
A1 |
Yodfat; Ofer ; et
al. |
May 5, 2011 |
Method for Selecting Bolus Doses and Bolus Delivery Patterns in a
Drug Delivery Device
Abstract
Embodiments of the present disclosure include methods, systems
and devices for selecting a bolus configuration and may include one
or more of providing a user interface for selection of one or more
user interface elements, where each element corresponds to a bolus
configuration of a drug, each element is spatially positioned
within a multi-dimensional space corresponding to at least three
dimensions and the element's position corresponding to each
dimension.
Inventors: |
Yodfat; Ofer; (Modi'in,
IL) ; Shapira; Gali; (Haifa, IL) ; Gescheit;
Iddo; (Tel Avis, IL) |
Family ID: |
41255505 |
Appl. No.: |
12/990179 |
Filed: |
April 28, 2009 |
PCT Filed: |
April 28, 2009 |
PCT NO: |
PCT/IL09/00454 |
371 Date: |
January 7, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61048856 |
Apr 29, 2008 |
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Current U.S.
Class: |
604/504 ;
604/66 |
Current CPC
Class: |
A61M 5/1723 20130101;
A61M 2205/3592 20130101; A61M 5/14248 20130101; G16H 10/40
20180101; A61M 2005/14296 20130101; A61M 2205/3569 20130101; A61M
2205/3576 20130101; G16H 20/17 20180101; A61M 2205/502 20130101;
A61M 2230/201 20130101; A61M 2205/52 20130101 |
Class at
Publication: |
604/504 ;
604/66 |
International
Class: |
A61M 5/168 20060101
A61M005/168 |
Claims
1.-60. (canceled)
61. A method for selecting a bolus configuration in a drug delivery
device for infusing a drug into a body of a user, the method
comprising: providing a fluid delivery system including a processor
having instructions operating thereon to enable the system and/or
allow the system to perform the steps of: receiving a current
glucose value of a user; receiving a value of a carbohydrate load
of a food intake to be consumed by the user; receiving a value of
one or more additional inputs; and automatically determining a
bolus configuration to be delivered to the user, wherein the bolus
configuration comprises an amount of a drug to be delivered and a
delivery pattern.
62. The method of claim 61, wherein determining the bolus
configuration comprises: determining the amount of drug to be
delivered based on the current glucose value and the carbohydrate
load; and determining the delivery pattern based on at least one of
the one or more additional inputs.
63. The method of claim 62, wherein the one or more additional
inputs is selected from the group consisting of: the glycemic index
(GI) of the intake, the content of the intake, glycemic load (GL)
of the intake, fat content of the food intake, fiber content of the
food intake, residual insulin (RI), and a physiological parameter
of the user.
64. The method of claim 61, wherein the bolus configuration is
determined based on previous bolus configurations.
65. The method of claim 61, wherein the value of at least one of
the current glucose value of the user, the carbohydrate load of a
food intake to be consumed and the one or more additional inputs
are represented as qualitative descriptive values.
66. The method of claim 65, wherein each qualitative descriptive
value comprises one or more value ranges of an input of the at
least one of the current glucose value of the user, the
carbohydrate load of a food intake to be consumed by the user and
the one or more additional inputs.
67. The method of claim 65, wherein the qualitative descriptive
values comprise small, medium and large.
68. The method of claim 61, wherein the amount of the drug to be
delivered does not exceed a pre-determined maximal overshoot and/or
minimal undershoot criteria.
69. The method of claim 68, wherein the maximal overshoot and/or
minimal undershoot criteria are configurable by the user.
70. The method of claim 61, further comprising providing a drug
delivery device infusing the drug according to the bolus
configuration.
71. The method of claim 61, wherein determining the bolus
configuration comprising: storing in a memory one or more bolus
configurations, each bolus configuration corresponds to a different
combination of values of three or more inputs, the three or more
inputs include the current glucose value of the user, the
carbohydrate load of a food intake to be consumed by the user and
the one or more additional inputs; indicating the one or more bolus
configurations to the user; and retrieving a bolus configuration
from the stored one or more bolus configurations based on user
selection of at least one of the one or more bolus configurations
via a user interface for determining the bolus configuration to be
delivered to the user.
72. The method of claim 71, wherein storing the one or more bolus
configurations comprises storing at least one grid of the one or
more bolus configurations, the at least one grid comprising three
or more dimensions, each dimension corresponds to one of the three
or more inputs and each bolus configuration correspond to a
different values combination of the three or more inputs.
73. The method of claim 72, wherein each grid of the at least one
grid is defined by one or more user parameters selected from the
group consisting of CIR, IS, TBG and RI.
74. The method of claim 72, further comprising providing a user
interface for presenting the at least one grid in a
multi-dimensional space presentation corresponding to the three or
more dimensions of the at least one grid, wherein each bolus
configuration is spatially positioned within the multi-dimensional
space in accordance to the different values combination of the
three or more inputs.
75. The method of claim 72, further comprising providing a user
interface for presenting the at least one grid in a two-dimensional
space presentation corresponding to two dimensions of the three or
more dimensions of the at least one grid, wherein each bolus
configuration is spatially positioned within the dimensional space
in accordance to the different values combination of the three or
more inputs.
76. The method of claim 61, further comprising providing a user
interface implemented in a remote control, a skin-securable
patch-pump delivering the drug according to the bolus
configuration, and optionally a glucometer providing the current
glucose value.
77. The method of claim 61, further comprising providing a
continuous glucose monitor (CGM) adopted for providing glucose
values.
78. A drug delivery system for infusing a drug into a body of a
user, the system comprising: a processor having instructions
operating thereon to enable the system to: receive a glucose value
of a user; receive a value of a carbohydrate load of a food intake
to be consumed by the user; receive values of one or more
additional inputs; and automatically determining a bolus
configuration, wherein the bolus configuration comprises an amount
of a drug to be delivered and a delivery pattern; and a drug
delivery device for infusing the drug to the user.
79. A method for selecting a bolus configuration in a drug delivery
device for infusing a drug into a body of a user, the method
comprising: providing a fluid delivery system including a processor
having instructions operating thereon to enable and/or perform the
steps of: receiving values of three or more inputs; storing, in a
memory, one or more bolus configurations, wherein each bolus
configuration corresponds to a different combination of three or
more input values and determining a bolus configuration by
retrieving the bolus configuration from the memory corresponding to
the three or more input values, the bolus configuration comprising
an amount of drug to be delivered and a delivery pattern.
Description
RELATED APPLICATION
[0001] The present application claims priority to U.S. provisional
application No. 61/048,856, filed Apr. 29, 2008, the entire
disclosure of which is herein incorporated by reference.
FIELD
[0002] Methods, systems and devices for sustained infusion of
fluids are described. Some embodiments describe a portable infusion
device and a method for selecting bolus dose and delivery pattern.
Some embodiments describe, for example, a skin securable insulin
dispensing device and a method for selecting bolus dose and
delivery pattern according to carbohydrate load and content of the
intake.
BACKGROUND
[0003] Diabetes mellitus is a disease of major global importance,
increasing in frequency at almost epidemic rates, such that the
worldwide prevalence in 2006 is 170 million people and predicted to
at least double over the next 10-15 years. Diabetes is
characterized by a chronically raised blood glucose concentration
(hyperglycemia), due to a relative or absolute lack of the
pancreatic hormone, insulin. Within the healthy pancreas, beta
cells, located in the islets of Langerhans, continuously produce
and secrete insulin according to the blood glucose levels,
maintaining near constant glucose levels in the body.
[0004] Much of the burden of the disease to the patient and to
health care resources is due to the long-term tissue complications,
which affect both small blood vessels (microangiopathy, causing
eye, kidney and nerve damage) and large blood vessels (causing
accelerated atherosclerosis, with increased rates of coronary heart
disease, peripheral vascular disease and stroke). The Diabetes
Control and Complications Trial (DCCT) demonstrated that
development and progression of the chronic complications of
diabetes are greatly related to the degree of altered glycemia as
quantified by determinations of glycohemoglobin (HbAlc). [DCCT
Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998;
352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N
Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining
normoglycemia by frequent glucose measurements and adjustment of
insulin delivery accordingly is of utmost importance.
[0005] Insulin pumps have been available which can deliver rapidly
acting insulin 24 hours a day, for example, through a cannula
inserted subcutaneously. The total daily insulin dose can be
divided into basal and bolus doses. Basal insulin dose or simply
basal insulin can be delivered continuously over 24 hours, and
keeps the blood glucose levels in an acceptable range between meals
and overnight. Diurnal basal rates can be pre-programmed or
manually changed according to various past or future daily
activities.
[0006] Insulin bolus doses or simply boluses can be delivered to
counteract carbohydrates loads before or after meals or during
episodes of high blood sugar levels. The amount of insulin (bolus
dose) can depend on several parameters that can be related to the
intake, blood sugar, and patient's specific parameters including
the following: [0007] an amount of carbohydrates (Carbs) in a meal
to be consumed, alternatively defined as "servings", wherein 1
serving=15 grams of Carbs; [0008] carbohydrate-to-insulin ratio
(CIR), i.e. the amount of carbohydrates balanced by one unit of
insulin; [0009] insulin sensitivity (IS), i.e. the amount of blood
glucose value lowered by one unit of insulin; [0010] current blood
glucose level (CBG); [0011] target blood glucose level (TBG), i.e.
the desired blood glucose level. TBG for most people suffering from
diabetes is in the range of 90-130 mg/dL; [0012] residual insulin
(RI), i.e. the amount of still active insulin remaining in the body
after recent bolus deliveries. This parameter can be relevant in a
situation when there is a short time interval between delivery of
boluses (e.g. less than 5 hours); and [0013] parameters that
influence carbs absorption and consequently rate of sugar rise in
blood such as Glycemic Index (GI), fat or fibers content, etc.
[0014] The insulin sensitivity (IS) can be determined, for example,
according to the so-called "2200 to 1600 rules" commonly used by
type 1 diabetes patients using rapid acting insulin (e.g.
Humalog.RTM., Novolog.RTM.). The user's IS can be determined by
dividing the value corresponding to a certain rule by the total
daily dose of rapid-acting insulin. For example, if the total daily
insulin dose is 40 units and the "1800" rule is used, the insulin
sensitivity factor would be 1800 divided by 40=45 mg/dl/unit. FIG.
1 illustrates the insulin sensitivity expressed as point drop per
unit of insulin corresponding to the various rules (adapted from
Using Insulin written by John Walsh .COPYRGT. 2003).
[0015] The carb to insulin ratio (CIR) can be determined, for
example, according to the so-called "450 to 500 rules" commonly
used by type 1 diabetes patients using rapid acting insulin (e.g.
Humalog.RTM., NovoLog.RTM.). The user CIR can be determined by
dividing the value corresponding to a certain rule by the total
daily dose of rapid-acting insulin. For example, if the total daily
insulin dose is 40 units and the 450 rule is used, the carb to
insulin ratio (CIR) would be 450 divided by 40=11 gram. FIG. 2
provides an example amount of carbs (in grams) that can be balanced
by 1 unit of insulin (CIR) according to various rules (adapted from
Using Insulin .COPYRGT. 2003).
[0016] The residual insulin can be determined according to the
pharmacokinetics of rapid acting insulin (e.g. Humalog.RTM.,
NovoLog.RTM.). FIG. 3 illustrates one example of amount of residual
insulin (in units) after 1-5 hours from a previous given bolus
(adapted from Using Insulin .COPYRGT. 2003).
[0017] The amount of insulin in the bolus to be delivered can be
established by calculations using equations that include the
abovementioned parameters, as described in U.S. Pat. No. 6,936,029
assigned to Medtronic MiniMed, or they can be selected by a method
for selection of the desired bolus dose, as described in co-owned,
co-pending U.S. patent application Ser. No. 12/051,400 and
International Patent Application No. PCT/IL2008/000380, the
disclosures of which are incorporated by reference in their
entireties.
[0018] The bolus delivery pattern refers to a rate or rates at
which the bolus dose is administered over time. The glycemic index
(GI) or fat content of the intake influence carbs absorption and
consequently bolus delivery time and pattern. The GI can be
expressed as a ranking system for carbohydrates contained in food
according to how they affect the blood glucose levels. Glucose, the
fastest-acting carbohydrate, is given a value of 100, and the other
carbs are ranked relative to that value. Ripeness, cooking time,
fiber, and fat content in the food can all impact GI. A low GI food
will release glucose more slowly and steadily. A high GI food
causes a more rapid rise in blood glucose. For example, FIG. 4
depicts different types of foods and their GI. A meal containing,
for example, a carbohydrate load having high glycemic index (e.g.
lemonade, white bread) would require insulin to be delivered
immediately to counteract the carbohydrates rapidly absorbed
through the gut. A meal containing a carbohydrate load having a low
glycemic index (e.g. milk, ice cream) would require insulin to be
delivered over a long period of time to counteract the slowly
absorbed carbohydrates.
[0019] Currently, most insulin pumps allow the user to program the
bolus delivery pattern. The most common delivery patterns are:
[0020] 1. immediate ("regular", "normal") bolus--the entire bolus
dose is delivered at the fastest pump delivery rate; [0021] 2.
extended bolus--the entire bolus is delivered over a long period of
time (e.g. 30 min-8 hours) at a constant rate; and [0022] 3.
combined bolus ("dual wave")--some of the bolus dose is delivered
as an immediate bolus and the rest of the bolus dose is delivered
as an extended bolus. Usually the ratio (in percentage) between the
immediate bolus portion and the extended bolus portion can be
selected by the patient, e.g. as described in U.S. Pat. No.
6,852,104 assigned to Smiths Medical MD (formerly Deltec
Medical).
[0023] In current devices, in order to adjust a bolus delivery
pattern, a user can program one or more of the following
parameters: duration of bolus delivery (for extended bolus and
extended portion of a combined bolus), ratio between the immediate
bolus portion and extended bolus portion (for combined bolus). In
practice, a user's decision about the bolus pattern is arbitrary
and based merely on intuition. Additional drawbacks associated with
conventional pumps that include means for programming bolus pattern
are: [0024] the necessity for data input which complicates the user
interface because it requires navigation through several displays
which are not user-friendly; and [0025] difficulties for young
children may to master data input since it is associated with
reading and typing alpha-numeric parameters.
[0026] The following definitions are provided for terms used
herein: [0027] "GI" (Glycemic Index) refers to a ranking system for
carbohydrates based on how they affect blood glucose levels. [0028]
"GL" (Glycemic Load") refers to the amount of carbs in a meal
multiplied by the GI of the meal divided by 100. [0029] "CIR"
(Carbohydrate to Insulin Ratio) refers to the amount of
carbohydrates balanced by one unit of insulin. [0030] "IS" (Insulin
Sensitivity) refers to the amount of blood glucose value lowered by
one unit of insulin. [0031] "Dose" or "bolus dose" refers to amount
of insulin administered to counteract carbohydrates in a meal (for
example 6 units (6 U)). [0032] "Delivery pattern" refers to the
pattern of delivery over time of administered dose (for example a
dose of 6 U may be delivered as follow--4 U in 2 hours and 2 U in
additional 4 hours). [0033] "Bolus" refers to the combination of
bolus dose and delivery pattern. [0034] "Grid" or "bolus grid"
refers to a matrix of 2 or more dimensions constructed of cells.
(for example a 3D matrix including the following axes: X--carbs,
Y--blood glucose, Z--glycemic index) Each grid is dedicated to a
different combination of parameters like CIR, IS, and target blood
glucose (TBG). [0035] "Cell" refers to one of many units comprising
a grid. Each cell represents a combination of parameters exhibited
on the different axes of the grid (e.g. combination of ranges of
GI, BG, and carb load).
SUMMARY
[0036] Embodiments of the present disclosure relate to techniques,
systems and devices are described for drug delivery according to
selected drug dose and drug delivery pattern. For example,
according to some embodiments, a drug delivery system and device is
provided which includes some embodiments of a user interface for
selection of one or more bolus configurations. In addition, one or
more user interface elements may be included where each user
interface element corresponds to a bolus configuration. Moreover,
in some embodiments, each element is spatially positioned within a
multi-dimensional space corresponding to at least three dimensions,
where the element's position, in some embodiments, corresponds to
each dimension. In such embodiments, each bolus configuration can
correspond to a bolus dose and a bolus delivery pattern. Moreover,
each bolus dose and/or each bolus delivery pattern can be
pre-determined. For example, some embodiments of the delivered drug
can be insulin and the drug delivery device can be an insulin pump.
The dimensions of the multi-dimensional space can represent at
least one or more of, and preferably at least three of, for
example, the current blood glucose levels, anticipated or current
carbohydrate load of the intake, glycemic index of the intake, and
glycemic load of the intake. The bolus dose can be recommended in
accordance with the carbohydrate load of the intake and the blood
glucose level of the user, and the bolus delivery pattern can be
recommended in accordance with the content of the intake (e.g. GI,
fiber content, fat content). The bolus dose and/or delivery pattern
can be further in accordance with one or more physiological
parameters. In some embodiments, the physiological parameters can
correspond to at least one of a heart rate, a ventilation rate, a
body temperature, insulin absorption characteristics (e.g. rate),
physical activity (e.g. exercise, steps of the user per period of
time.
[0037] In some embodiments, the delivery pattern can be recommended
according to the GI of the intake. The bolus delivery pattern can
be recommended in accordance with a correction bolus. In some
embodiments, the measurements of the dimensions can be represented
as qualitative descriptive parameters. The qualitative descriptive
parameters can comprise one or more ranges. The ranges can be
selected, for example, from the group of small, medium and
large.
[0038] The drug delivery system and/or device can further comprise
a glucometer. The user interface of the drug delivery device can be
implemented in the system via a remote control unit and the drug
can be delivered using a skin securable patch unit. The glucometer
can be located in the remote control unit of the device and/or in
the skin securable patch unit of the device. The drug delivery
device can also comprise a continuous glucose monitor. The
continuous glucose monitor can be located in the patch unit of the
device, and/or in the remote (in some embodiments, components of
the continuous glucose monitor may be provided in the remote).
[0039] In some embodiments, the insulin bolus delivery pattern can
be determined as a function of a fat content of the food intake.
The insulin bolus delivery pattern can also be established as a
function of a fiber content of the food intake. In some
embodiments, the bolus doses do not exceed a pre-determined maximal
overshoot and minimal undershoot criteria. The maximal overshoot
and minimal undershoot criteria can be defined by the user.
[0040] In some embodiments, the drug delivery system and/or device
can also comprise a second user interface for displaying user
interface elements positioned within a two-dimensional space and
the two dimensions of the two-dimensional space correspond to at
least two dimensions of the multi-dimensional space. In some
embodiments, the drug delivery device can also comprise a
disposable part and a reusable part. It can comprise a skin
securable cradle unit allowing disconnection and reconnection of
the patch unit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0041] FIG. 1 is a table for calculating insulin sensitivity (point
drop per unit of insulin) according to various rules.
[0042] FIG. 2 is a table for calculating CIR (carbs in grams
balanced by 1 unit of insulin) according to various rules.
[0043] FIG. 3 is a table for calculating Residual Insulin (in
units) after 1-5 hours from a previous given bolus.
[0044] FIG. 4 is a chart depicting different types of foods and
their GI ranking system based on how they affect blood glucose
levels.
[0045] FIG. 5 provides one example of a three-dimensional grid,
where carbohydrate intake ranges are presented on the "x" axis of
the grid, blood glucose levels (BG) are presented on the "y" axis
of the grid, and GI levels are presented on the "z" axis of the
grid, according to some embodiments of the present disclosure.
[0046] FIG. 6 provides one example of a 2D bolus-grid that
illustrates delivery patterns selected for High BG range and
various values of GI and Carb loads according to some embodiments
of the present disclosure.
[0047] FIG. 7 is a diagram illustrating an example of an insulin
infusion system comprising an insulin dispensing unit and a remote
control unit that can be fitted with a bolus selector, according to
some embodiments of the disclosure.
[0048] FIG. 8 is a flow chart representing some embodiments of a
method for selecting a recommended insulin bolus (dosage and
delivery pattern) according to some embodiments of the present
disclosure.
[0049] FIG. 9 is a flow chart representing another example of a
method for selecting a recommended insulin bolus according to some
embodiments of the present disclosure.
[0050] FIG. 10 illustrates an example of a three dimensional
bolus-grid with insulin bolus dosages and delivery patterns
corresponding to carb load, GI, and current blood glucose levels
according to some embodiments of the present disclosure.
[0051] FIGS. 11a-d illustrate "two dimensional" slices of the three
dimensional bolus-grids with insulin bolus dosages and delivery
patterns corresponding to carb load, GI, and current blood glucose
levels, yielding a 2D chart, according to some embodiments.
[0052] FIG. 12 provides one example of a bolus selector user
interface, including a series of window/display flow, according to
some embodiments of the present disclosure.
[0053] FIGS. 13a-b provide another example of a bolus selector user
interface, including, for example, the windows shown in the
figures, where the carb load of the intake and the GI of the intake
are used for selecting the bolus, according to some embodiments of
the present disclosure.
[0054] FIG. 14 illustrates another example of a bolus selector user
interface, where the carb load of the intake and the GI of the
intake are used for selecting the bolus, for example, according to
some embodiments of the disclosure.
[0055] FIG. 15 illustrates a still further example of the bolus
selector user interface where the carb load of the intake and the
GI of the intake are used for selecting the bolus, according to
some embodiments of the disclosure.
[0056] FIGS. 16a-c provide some examples of an insulin infusion
system/device containing blood glucose monitor providing blood
glucose (BG) readings for the bolus selector, according to some
embodiments of the present disclosure.
[0057] FIGS. 17a-b provide examples of insulin infusion
system/device containing various subcutaneous glucose monitors
providing blood glucose readings (BG) for the bolus selector,
according to some embodiments of the present disclosure.
[0058] FIG. 18 is a block diagram illustrating data acquisition
modes that, in some embodiments, can be used by the bolus
selector.
[0059] FIG. 19 illustrates another embodiment of the bolus selector
that can be located in a remote control unit and/or PC, according
to some embodiments of the present disclosure.
[0060] FIGS. 20a-c illustrate examples of 2D slices derived from a
3D bolus grid with its corresponding minimal undershoot and maximal
overshoot BG values, according to some embodiments of the present
disclosure.
[0061] FIG. 21 illustrates examples of a plurality of bolus
delivery patterns that can be recommended to the user by the bolus
selector according to some embodiments of the present
disclosure.
DETAILED DESCRIPTION
[0062] Systems, devices and methods for selecting, for example, a
drug bolus dose and a bolus delivery pattern are provided herein.
In some embodiment, the device can comprise a user interface for
selection of one or more bolus configurations. The bolus
configurations can be selected using one or more user interface
elements (for example).
[0063] In some embodiments, each user interface element can
correspond to a bolus configuration. For example, each user
interface element can be spatially positioned within a
multi-dimensional space. In some embodiments, the multi-dimensional
space corresponds to at least three dimensions. The spatial
position of the user interface elements within the
multi-dimensional space can correspond to each dimension.
[0064] In some embodiments, a three-dimensional matrix of cells can
be used to recommend pre-determined insulin boluses that are
pre-determined for each combination of carbs load of the intake, GI
of the intake and BG of the user. In that implementation, each cell
can represent a user interface element and can correspond to a
bolus configuration (for example. These bolus configurations can be
pre-determined and stored in a memory of the bolus selector. In
some embodiments, these bolus configurations can be predetermined
by a manufacturer, a parent, a physician and/or by a user. The
pre-determined database can be displayed by the bolus selector
graphically as a plurality of cells arranged in a 3D grid,
referred-to as a "bolus-grid."
[0065] FIG. 5 illustrates a simplified example of a 3-dimensional
grid of the bolus selector. Carbohydrate intake ranges are
presented on the "x" axis of the grid, blood glucose levels (BG)
are presented on the "y" axis of the grid, and GI levels are
presented on the "z" axis of the grid. Any other parameter that,
for example, expresses a characteristics of the intake that
determine its absorption (e.g. fat content, fiber content, cooking
time), can be presented on the "z" axis of the grid. The bolus-grid
can also allow the user to select a cell from within the bolus-grid
depending on a combination of ranges of BG, carbohydrate load of
the intake, and GI of the intake (for example).
[0066] Accordingly, in some embodiments, the dose of the bolus can
be selected from the pre-determined combination ("grids") of
carbohydrate loads and BG that pre-define a value of insulin dose.
For example, the intersection of the "x" (carb load) and "y" (BG)
axes of the grid can corresponds to a pre-determined bolus
dose.
[0067] The delivery pattern of the bolus can be selected according
to the meal content. For example, the glycemic index of the meal.
Thus; for example, the intersection of the "z" axis (GI) with the
bolus dose (as derived from the intersection of the "x" and "y"
axes), correspond to the final selected bolus--dose and delivery
pattern. The following list provides a few examples of the delivery
patterns: [0068] 1--entire dose delivered immediately; [0069]
2--portion of dose delivered immediately and the rest over 2 hours;
[0070] 3--portion of dose delivered immediately and the rest over 4
hours; [0071] 4--entire dose delivered over 6 hours.
[0072] In some embodiments, the user can also select, for example,
the insulin bolus dose from a pre-determined three dimensional grid
of insulin boluses, corresponding to given ranges of blood glucose
(BG) values (e.g. BG<100, 100<BG<200, 200<BG<300,
300<BG), ranges of carbohydrate loads (e.g. carbs<45,
45<carbs<105, carbs<105) and given ranges of glycemic
loads (e.g. GL<10, 11<GL<19, GL>20). The delivery
pattern can be determined, for example, according to the glycemic
load of the intake.
[0073] According to some embodiments, a three dimensional bolus
grid may comprise BG ranges, carb load ranges and GI ranges. For
example, the GL can be automatically calculated according to the
selected GI range and carb load range. The delivery pattern can be
subsequently selected according to the calculated GL, for example.
GL can also be pre-determined for each combination of GI and carb
load.
[0074] According to some embodiments, the carb load ranges can be
presented on the axis of the grid in servings instead of grams. One
serving of a carbohydrate food typically contains 15 grams of
carbohydrate (e.g. serving<3, 3<servings<7, serving>7),
rather than distinct values.
[0075] In some embodiments, the bolus selector can include the
ability for a user to insert the numerical value of blood glucose
instead of selecting a range of BG levels. The BG numerical value
can then be ascribed by the bolus selector to the relevant range of
BG levels. For example, if the user inserts a BG of 221 mg/dL, the
bolus selector automatically assigns the numerical value to the
relevant BG range: 210-230 mg/dL.
[0076] In some embodiments, the pre-determined insulin doses that
correspond to a selected current BG range and carbohydrate load
intake range can be pre-determined according to a formula which
takes into consideration the user's CIR, IS, and target blood
glucose (TBG) as constant coefficients. The bolus selector can
comprise a plurality of grids, and each grid can correspond to a
different combination of user specific parameters that may include
IS, CIR, and TBG.
[0077] The plurality of 3D bolus grids can be stored in the memory
of the bolus selector and each grid can correspond to a different
combination of IS, CIR, and TBG. By virtue of this provision, the
bolus-grid doses are adjusted to the user's individual insulin
needs as dictated by the user's specific CIR, IS, and TBG. Each
grid in the bolus selector can be configured for a different
combination of CIR, IS, and TBG. The user can insert the TBG, CIR,
and IS values when initially setting the bolus selector in order
for the appropriate grid to be retrieved.
[0078] Alternatively, according to some embodiments, the user can
provide a "rule" and a total daily dose (TDD), and the CIR and IS
value can subsequently be obtained (as shown in FIGS. 1 and 2). For
example, the user can provide the following information in the
initial setting: [0079] "Rule" for CIR=500 [0080] TDD=25 U [0081]
"Rule" for IS=2000
[0082] Using the example values presented above and the tables on
FIG. 1 and FIG. 2, the CIR value is 20 g/U (CIR=500/25) and the IS
value is 80 mg/dL/U (2000/25).
[0083] In some embodiments, additional parameters, such as time
lapsed from last meals and amount of previous bolus doses, can be
taken into consideration for recommending a final bolus dose. For
example, the amount of residual insulin can be subtracted from the
insulin dose recommended by the bolus selector, resulting in a
lower recommended bolus dose (e.g. if the user has 2 U of residual
insulin from previous boluses and according to the bolus selector
grid an insulin dose of 4 U is required to balance a contemplated
meal, than the final recommendation would be 4-2=2 U).
[0084] In some embodiments, the recommended bolus (dose and
delivery pattern) can be selected by the user from a displayed
three dimensional graph wherein one axis can indicate ranges of
current BG levels, one axis can indicate ranges of carbohydrate
loads, and a third axis can indicate ranges of GI or GL, for
example.
[0085] In some embodiments, the recommended bolus dose can be
automatically selected by the bolus selector upon inputs of at
least a range of current BG levels, a range of carbohydrate load,
and a range of GI or GL. That is, the cell of the grid that is the
intersection of the parameters inputted by the user is
automatically selected.
[0086] In some embodiments, the user can accept the bolus
automatically selected and recommended upon inputs of at least a
range of current BG levels, a range of carbohydrate load, and a
range of GI or GL, and can deliver a bolus accordingly. In
addition, the automatically selected bolus can be delivered without
providing a notification to a user interface. In such an
embodiment, the user can be notified prior to bolus administration
and can suspend delivery or select an alternative dose and/or
delivery pattern.
[0087] In some embodiments, a bolus selector can be constructed of
"n" dimensions. For example, each dimension can represent an
independent parameter that influences the optimal bolus to be
delivered. The dose and delivery pattern of the bolus can thus be
selected from pre-determined grids of "n" dimensions. For example,
a 4 dimensional grid can comprise a "v" axis representing the
user's BG, a "w" axis representing the carbohydrate load, a "x"
axis representing the GI of the intake, a "y" axis representing the
fat content of the intake, and a "z" axis representing the fiber
content of the intake. The intersection of all 4 axes correspond to
the final selected bolus--dose and delivery pattern.
[0088] Some embodiments according to the present disclosure
disclose a portable drug delivery system/device that can deliver
therapeutic fluids into the body (i.e. insulin). In some
embodiments, it can also monitor bodily analyte levels (i.e.
glucose). The drug delivery system can comprise a dispensing patch
unit and, in some embodiments, can be combined with a remote
control unit, which communicates with the dispensing patch unit and
allows programming of therapeutic fluid delivery, user input and
data acquisition. In another embodiment, programming can be carried
out manually by operating buttons located on the dispensing patch
unit.
[0089] The dispensing patch unit can be composed of two parts--a
disposable part and a reusable part. The disposable part can
contain reservoir, outlet port, and other relatively inexpensive
components. The reusable part can contain electronics (PCB,
processor, etc), driving mechanism (e.g. a motor, gears) and other
relatively expensive components (e.g. occlusion sensor). A cradle
unit can be provided, which is an element (e.g., a substantially
flat sheet of material) that adheres to the skin and allows
disconnection and reconnection of the patch unit (sometimes
referred to as a dispensing unit or dispensing patch unit) upon
patient discretion. After attachment of the cradle unit to the
skin, a cannula can be inserted into the subcutaneous compartment
through a dedicated passageway in the cradle unit. The described
drug delivery device can be provided with a software feature
enabling selecting an appropriate bolus dose and delivery
pattern.
[0090] In some embodiments, the drug delivery device can employ a
simplified, easy to use method for selecting appropriate insulin
bolus from a plurality of pre-determined insulin bolus doses and
bolus delivery patterns. For example, such method can be used with
a device dedicated for selection of the appropriate bolus, or it
can be implemented in a glucometer, a continuous glucose monitor,
an infusion pump, a delivery pen, a PC or any other device used by
the diabetes patient.
[0091] In some embodiments, the drug delivery system/device can
continuously monitor body glucose levels and can concomitantly
deliver insulin boluses. Some embodiments of the present disclosure
can provide a device comprising a miniature skin securable insulin
dispensing patch that can deliver insulin boluses according to
bolus selecting method.
[0092] Some embodiments can provide a device that includes a skin
securable dispensing patch unit and a method to select an insulin
bolus. The dispensing patch unit can be attached to the skin
directly, or by virtue of a cradle unit. Some embodiments provide a
device with a dispensing patch unit that can be disconnected and
reconnected and a method to select an insulin bolus. Some
embodiments provide a device comprising a miniature skin securable
patch that can continuously dispense insulin and monitor body
glucose concentration levels and a method to select an insulin
bolus. In some embodiments, the patch can be secured using an
adhesive substance or a strap.
[0093] Some embodiments provide a device that dispenses insulin
according to monitored glucose levels (semi closed loop system) and
a method to select an insulin bolus. In some embodiments, the
device can comprise insulin dispensing patch unit that can be
remotely controlled and a method to select an insulin bolus.
[0094] In some embodiments, the method(s) for selecting a bolus can
employ at least one of the following parameters: current blood
glucose levels (BG), carbohydrate load of the intake (Carb),
glycemic index of the intake (GI), glycemic load of the intake
(GL).
[0095] In some embodiments, the method for insulin bolus delivery
can be based on selection of the optimal dose from a database of
pre-determined values of bolus doses and on selection of the
optimal bolus delivery pattern from a database of pre-determined
bolus delivery patterns.
[0096] In one embodiment, the user can select the insulin bolus
dose from a pre-determined three dimensional grid of insulin
boluses, corresponding to ranges of blood glucose (BG) values (e.g.
BG<100, 100<BG<200, 200<BG<300, 300<BG), ranges
of carbohydrate loads (e.g. carbs<45, 45<carbs<105,
carbs<105) and ranges of glycemic indexes (e.g. GI<55,
56<GI<69, GI>70).
[0097] According to some examples, ranges of blood glucose level,
glycemic index of the intake, and carbohydrate load of the intake
are presented on the axes of the grid as a qualitative descriptive
parameter (QDP) (e.g. high/medium/low BG, high/intermediate/low GI,
small/medium/large carb load).
[0098] In some embodiments, the bolus selection method can be
implemented in an insulin infusion system comprising an insulin
dispensing patch unit and a remote control unit, where a blood
glucose sensing apparatus (e.g. glucometer) can be integrated in
the remote control unit (while it may also be integrated into the
patch unit, for example). In one such embodiment, the dispensing
patch unit can be composed of two parts, a reusable part that can
contain all electronic and driving elements and a disposable part
that can contain insulin reservoir and power supply. The blood
glucose sensing apparatus (e.g. glucometer) can alternatively be
integrated in the reusable part of the patch unit of the
device.
[0099] In some embodiments, the blood glucose sensing apparatus
such as a glucometer, can be dedicated for measuring glucose
concentrations. For example, it can be implemented as a
"stand-alone" device, an element in the remote control, which
receives blood strips, a sensor in the housing of the dispensing
unit such as electrodes disposed on the cannula, etc, as disclosed
in co-owned, co pending U.S. patent application Ser. Nos.
11/706,606 and 11/963,481, in International Patent Application Nos.
PCT/IL2007/001579 and PCT/IL2008/001521, the disclosures of which
are incorporated by reference in their entireties. It can also be
implemented as a continuous glucose monitor (CGM). It can use
various techniques such as an electrochemical means (e.g.
electrochemical sensors, electrodes, enzymes, nanoparticles), an
optical means (e.g. optical sensors, optical fibers, reflectors,
mirrors, lens), an acoustic means etc. It can measure the glucose
level in the blood, interstitial fluid ("ISF") or any other
relevant compartment of the patient's body.
[0100] The bolus selector can be implemented in the remote control
unit of the insulin infusion system. The bolus selector can also be
implemented in the reusable part of the dispensing patch unit of
the device of the system. The bolus selector can be implemented in
both the reusable part of the dispensing patch unit of the device
and the remote control unit of the system.
[0101] In one embodiment, the bolus selection method can be
implemented in the dispensing patch unit that can continuously
monitor body glucose levels and can concomitantly deliver insulin
into the body. The dispensing patch unit can comprise a reusable
part and a disposable part. The insulin dispensing and glucose
sensing capabilities can be combined into a semi closed loop
system, where a processor-controller apparatus regulates the
dispensing of basal insulin according to the sensed glucose
concentration. The meal boluses can be controlled by the bolus
selector.
[0102] The bolus selector can be implemented in the remote control
unit of the system, and/or can also be implemented in the reusable
part of dispensing patch unit of the device. In some embodiments,
the bolus selection method can be implemented in a device for
sensing blood glucose (e.g. glucometer) or a device for
continuously sensing subcutaneous interstitial fluid glucose or for
any other glucose sensing device (i.e. non invasive glucose
sensors, iontopheresis based sensors, etc.)
[0103] In some embodiments, the delivery pattern of the insulin
dose can be selected by the user according to the glycemic index
(GI) or glycemic indexes of the carbohydrates of the intake. The
delivery pattern of the insulin dose can also be selected by the
user according to the glycemic load (GL) of the carbohydrates
contained in the intake. The GL of a meal is defined as GL=(GI*carb
load)/100. The duration of insulin action (DIA) can be affected by
the size of the insulin dose, with higher doses correlated with a
longer DIA. Therefore, the size of the dose which reflects the
carbohydrate load of the meal, should also influences the delivery
pattern (long DIA requires a longer delivery profile and vice
versa).
[0104] The delivery pattern of the insulin dose can alternatively
be selected by the user according to additional characteristics of
the intake such as the fat content, fiber content, or cooking time.
For instance, a high fat meal will slow down glucose absorption
from the gut and thus require a relatively long bolus delivery
pattern to match the glucose absorption rate.
[0105] FIG. 6 illustrates one example of a 2D bolus-grid that
illustrates delivery patterns selected for High BG range and
various values of GI and Carb loads. The user can insert a
numerical BG value (that can automatically be ascribed by the bolus
selector to the relevant range of BG levels) or select a BG range
and subsequently a 2D matrix, as shown in the figure, can be
displayed to the user. For example, if the user's measured BG is
225, then the pre-determined bolus grid matrix corresponding to the
High BG can be displayed.
[0106] FIG. 7 illustrates an insulin infusion device (1000)
comprising a dispensing patch unit (hereinafter "patch unit")
(1010), which can be adhered to the user's skin (5), and a remote
control unit (1008), which communicates with the dispensing patch
unit (1010), allowing programming, user inputs and data
acquisition. The patch unit (1010) can be removably connected to a
cannula (6) that can penetrate the skin (5) to allow delivery of
insulin to the patient. The patch unit (1010) can be attached to a
dedicated cradle unit (20) that can be configured as a
substantially flat sheet adhered to the user's skin (5). The cradle
unit can allows connection/disconnection of the patch unit (1010).
An exemplary embodiment of this arrangement is discussed in a
co-owned, co-pending U.S. patent application Ser. No. 12/004,837
and International Patent Application No. PCT/IL07/001578, the
disclosures of which are herein incorporated by reference in their
entireties.
[0107] Manual inputs can be effected by one or more
buttons/switches (1011) located on the dispensing patch unit
(1010). The dispensing patch unit (1010) can be fitted with one
housing or two housings comprising reusable (1) and disposable (2)
parts as shown in co-owned, co-pending patent application U.S. Ser.
No. 11/397,115 and International Patent Application No.
PCT/IL2009/000388, the disclosures of which are incorporated by
reference in their entireties. The remote control unit (1008) can
contain a bolus selector (2000), which can be implemented as a
software feature. The remote control unit (1008) can comprise a
processor (2010), a memory (2020), an input means (2030) such as
buttons, switches, touch-screen, voice/audible commander/receiver,
a display (2040) and other indication means such as, for example,
audible means (e.g. buzzer) and/or vibration means (e.g. vibrator).
The input means (2030) can be provided for the bolus selector
(2000) and for dispensing patch unit (1010) programming.
[0108] Options for insulin bolus administration can be provided by
the bolus selector (2000) on the display (2040) as a three
dimensional grid with cells containing recommended pre-determined
bolus dosages and recommended pre-determined delivery patterns. The
appropriate cell and corresponding insulin dose and delivery
pattern can be selected from a predetermined 3D table according to,
for example, at least one parameter selected from blood glucose,
carb content, and GI or GL. A 3D bolus grid can, for example,
include the following axes: X--carbs, Y--blood glucose, Z--glycemic
index. For example, each intersection of the X and Y axes can
define a bolus dose. Each intersection of a bolus dose with the Z
axis can define the delivery pattern at which the bolus dose is to
be administered. Such a table with recommended pre-determined bolus
dosages and recommended pre-determined delivery patterns will be
referred-to further as a "bolus-grid" and any combination of two or
more grids will be referred-to further as a "bolus-grid cell" or a
"cell".
[0109] The bolus-grid cells can comprise pre-determined bolus doses
and delivery patterns corresponding to optional combinations of the
current blood glucose level, the user's approximation of the carb
load in the consumed or to be consumed meal, and the user's
approximation of the GI or the GL of the consumed or to be consumed
meal (examples of such grids are shown in FIGS. 5 and 6). In some
embodiments, the bolus-grids can be pre-determined and stored in
the memory of the bolus selector (2000).
[0110] In some embodiments, the bolus selector (2000) can contain
many 3D bolus grids. Each grid can correspond to a specific
combination of the target BG, IS value, and CIR. The user's
specific bolus-grid or grids (e.g. a user has different TBG
throughout the day) can be retrievable from the bolus selector
(2000) memory, for example. In some embodiments, the bolus selector
can be located in the reusable part of the dispensing patch
unit.
[0111] FIG. 8 illustrates a block diagram representing one example
of the method for selecting a recommended insulin bolus dosage and
a recommended delivery pattern. For example, this method can be
implemented by the bolus selector. In some embodiments, for
selection of the user specific bolus, a three dimensional grid with
pre-established insulin boluses can be retrieved from the memory of
the bolus selector. A plurality of grids can also be saved in the
memory of the bolus selector. Each grid can be suitable for a
different combination of user specific parameters, such as IS, CIR,
and TBG. The appropriate grid can be retrieved from the memory upon
user input of these parameters.
[0112] The bolus can be pre-determined for each combination of carb
load, GI, and blood glucose level in each stored bolus-grid. The
user can select the appropriate combination of these parameters,
input them into the bolus selector and, in some embodiments,
automatically retrieve a cell of the grid corresponding to this
combination. This cell can provide a bolus describing a dose and a
delivery pattern from the retrieved bolus-grid. The appropriate
bolus should correspond to a combination of the contemplated carb
intake (load and GI) and results of the actual measurements of the
blood glucose level. The measurements of the blood glucose level
can be inputted by the user or automatically obtained from a
glucometer or a continuous glucose monitor (CGM) that, in some
embodiments, communicates with the bolus selector. The bolus
delivery patterns can also be pre-determined according to a series
of tests for tailoring the GI related delivery bolus to a user.
These tests can be performed by the user during the initial setting
of the infusion device.
[0113] In some embodiments, IS, CIR and target BG values
(designated in FIG. 8 as 201,201',201'', for example) can be loaded
in the bolus selector by the patient, and the patient's specific
bolus-grid can be retrieved accordingly at (202) and displayed to
the patient. At 203, the recommended bolus from the displayed
bolus-grid can be selected. The selection can be based on the
contemplated carb load of the intake, GI of the intake and/or blood
glucose (BG) level (for example). These parameters can be presented
within the bolus-grid, in this example "x" axis--carb ranges, "y"
axis--BG ranges, and "z" axis--GI ranges. Selection of the relevant
combination of these parameters is designated as (204).
[0114] Blood glucose levels can be obtained from any suitable
glucose sensor e.g. glucometer, continuous subcutaneous glucose
sensor etc. Glucose measurements can be carried out immediately
before the bolus selection. Contemplated carb load and GI can be
assessed by the user.
[0115] In some embodiments, for example as shown at (208), the
residual insulin value can be obtained from the previous bolus
doses and elapsed time (e.g., as shown in FIG. 3). The input of the
residual insulin value can trigger subtraction of the residual
insulin content from the recommended bolus dose. For example, as
illustrated in FIG. 3, if 2 units of insulin were administered 1
hour prior to administering of the current bolus, 1.6 units of
insulin were not absorbed and reside in the body (residual
insulin=1.6). Therefore, the bolus suggested by the bolus selector
should be lower by 1.6 units than the pre-determined bolus with no
residual insulin (residual insulin=0). Moreover, if 2 units of
insulin were administered 1 hour prior to the current bolus (1.6 U)
and 3 units were administered 3 hours prior to the current bolus
(RI=1.2 U), 2.8 U (1.2+1.6) should be subtracted (for example). In
some embodiments, the residual insulin does not affect the delivery
bolus pattern, just the dose. Various infusion devices can be used
for insulin delivery (e.g., insulin pumps, injection pens,
delivery/dispensing devices, etc). Insulin residue values can be
displayed periodically or at the user's discretion (for
example).
[0116] According to another embodiment, the RI can be an additional
dimension of the bolus grid, for example. That is, an axis with
ranges of RI can also be a parameter in determining the cell with
the recommended bolus dose and delivery pattern. In such an
embodiment, there is no subtraction of RI but rather a selection of
RI.
[0117] At (204), the user can accept the selected bolus dose and
delivery pattern. In some embodiments, for example as shown at 206,
the user can manually modify the selected bolus by navigating
across the bolus-grid and retrieving an alternative bolus
(alternative dose and/or delivery pattern).
[0118] At (205), a user can substitute the selected bolus with an
alternative bolus (not from the bolus-grid), according to some
embodiments. Irrespective of whether the bolus is selected by the
bolus selector at (204), or modified and selected at (206), or
chosen at (205), the bolus delivery can be initiated at (209) by a
command transmitted from the remote control unit and/or by manual
bolus buttons that can be located on the dispensing patch unit.
[0119] In one embodiment, the axes (e.g. carbohydrate intake ranges
are presented on the "x" axis of the grid, blood glucose levels are
presented on the "y" axis of the grid, and the GL levels are
presented on the "z" axis of the grid) of the 3D bolus-grids can
comprise preset ranges of carb load, ranges of GL, and ranges of
blood glucose level. The boluses can be pre-determined for each
combination of carb load range, GL range and a range of blood
glucose level.
[0120] In some embodiments, the axes of the 3D bolus-grids can
comprise ranges of carb load, ranges of GI and ranges of blood
glucose level. In some embodiments, the ranges of GL are not
pre-determined, but are calculated by the bolus selector from the
selected range of GI and range of carb load. For example, the
boluses can be pre-determined for each combination of carb load
range, calculated GL range, and range of blood glucose level.
[0121] FIG. 9 illustrates a block diagram of a bolus selector,
according to some embodiments, that can be used for implementing
the method for selecting a recommended insulin bolus. At 301, for
example, the bolus selector can be preset according to the user's
individual parameters--i.e. the following parameters are set:
carbohydrate to insulin ratio (CIR) and insulin sensitivity (IS).
These parameters can be obtained by the "450-500 rules" and "1600
to 2200 rules" respectively (e.g. as illustrated on FIGS. 1 and
2).
[0122] In some embodiments, the user can preset an additional
parameter, namely the target blood glucose (TBG) levels. TBG can
vary throughout the day and this parameter can be configurable to
allow retrieval of the pre-meal appropriate bolus-grid. The IS
value and the CIR can also vary throughout the day and these
parameters can also be configurable to allow retrieval of the
pre-meal appropriate bolus-grid.
[0123] In some embodiments, the CIR and IS values can repeatedly be
adjusted according to the recently (e.g. last days) stored bolus
data. This step can be designated as step (307). CIR and IS values
can be selected from Tables 2 and 1 respectively by choosing the
appropriate rule and a total daily dose (TDD), which, in on
implementation, can be an average from the last days' usage data.
For example, if the 500 and 1800 rules are selected and the average
TDD is 50 IU/day, the CIR and IS are 10 gram/unit and 36 mg/dl/unit
respectively. After adjustment of the CIR and IS values,
appropriate bolus-grids corresponding to the revised IS and CIR
parameters can be retrieved by the bolus selector.
[0124] In some embodiments, the rules applied can also be
repeatedly adjusted according to the last days stored bolus data.
For example, the rules can be associated with the percentage of the
basal dose from the total daily dose (TDD). The optimal rules to be
applied can, therefore, be determined by establishing the
percentage of the basal dose from the stored total daily dose
(TDD). For example, if the basal dose is 50% of the TDD, the
optimal applied rules should be the "500 rule" and "2000 rule" for
the CIR and IS respectively. If the basal dose is 40% of the TDD,
the applied rules should be the "450 rule" and "1800 rule" for the
CIR and IS respectively. If the basal dose is 60% of the TDD, the
applied rules should be the "550 rule" and "2200 rule" for the CIR
and IS respectively.
[0125] Step 302 can be an optional feature of the bolus selector
according to some embodiments. This feature which can shorten the
time of the selection process by presenting the average bolus dose
and delivery pattern used during a selected time interval in the
last few days to the user. For example, the day can be divided into
five time intervals (e.g. 6:00-10:00, 10:00-14:00, 14:00-18:00.
18:00-22:00, 22:00-6:00) and the average of the total amount of
insulin and the most prevalent delivery pattern delivered during
the corresponding time interval in the last several days would be
the featured value (302). The bolus selector can thus indicate a
bolus even prior to loading the BG, carbs load and GI. This value
can be displayed as a stand alone parameter or as a first
preferable choice or marked cell within the 3D bolus grid and it
can be used as an adjunct recommendation for bolus selection.
[0126] The defined time interval can also be selected from a
certain basal profile (e.g. by averaging the boluses given between
6 to 10 am in the last 7 "weekend" profiles), for example.
[0127] In one embodiment, the averaged bolus dose can be presented
to the user if the standard deviation of the bolus dose is
insignificant. If a significant deviation is noted, the averaged
bolus dose value is not presented. The bolus selector can also
alert the user if the selected bolus differs from the average value
by, for example, a considerable amount. A considerable amount can
be defined as percentage of the total bolus dose. Alternatively, a
considerable amount can be individually defined for each user
according to the user's IS value. For example, a deviation of 1
unit for a user with an IS of 90 mg/dL/U may cause a BG drop of 90
mg/dL, wherein a deviation of 1 unit for a user with an IS of 10
mg/dL/U may cause a BG drop of 10 mg/dL.
[0128] The data referring to the time, the dosage, and the delivery
pattern of the previously administered boluses can be stored in the
memory (2020), as shown in FIG. 7, and can be displayed
periodically or at the user's discretion, according to some
embodiments of the present disclosure.
[0129] At 303, the bolus dose from the retrieved bolus-grid can be
selected. In this example, "x" axis represents carb ranges, "y"
axis represents BG ranges, and "z" axis represents GI ranges (204).
Blood glucose levels can be obtained at the step (302a) from any
suitable glucose sensor e.g. glucometer, continuous subcutaneous
glucose sensor etc. The carb load and GI can be evaluated by the
user at steps (302b) and (302c) respectively. At 308, the residual
insulin content can be subtracted from the predetermined bolus
doses.
[0130] In some embodiments, the user can accept a selected bolus
(304), manually choose the bolus value (306) and/or select an
alternative bolus from the bolus grid (309). Irrespective whether
the bolus is directly selected with the aim of the bolus selector,
or subsequently modified and selected while taking into
consideration the administering history, the bolus delivery at the
step (310) can be initiated by transmitting a command from the
remote control unit and/or by manual input by virtue of bolus
buttons, in some embodiments, located on the dispensing patch
unit.
[0131] A bolus selected from the bolus-grid can also be delivered
automatically and tactile, audible or vibrational alerts can be
used to notify the patient prior to the bolus delivery, after the
bolus delivery or if the delivery is suspended. In one embodiment,
the dispensing device can be used for delivery of insulin and it
can be configured as a skin adhered pump. In another embodiment,
other devices for insulin delivery can be used (e.g. insulin pumps,
injection pens, etc.).
[0132] FIG. 10 illustrates an embodiment of a three-dimensional
bolus-grid with pre-determined insulin bolus dosages and with
delivery patterns corresponding to given carb load, GI, and current
blood glucose measurements. The 3D grid in the FIG. 10 illustrates
a bolus-grid which can be suitable, for example, for a patient with
a high carbohydrate-to-insulin ratio (CIR) (e.g. 40 g/unit), high
insulin sensitivity (IS) (e.g. 100 mg/dL/unit), and normal gastric
emptying and glucose absorption rate.
[0133] FIGS. 11a-d provide some examples of "two dimensional"
slices of three dimensional bolus-grids with pre-determined insulin
bolus dosages and with pre-established delivery patterns
corresponding to a given carb load, GI, and current blood glucose
measurements. For example, the 2D slice illustrated in the FIG. 11a
corresponds to a low GI meal. For example, when a low GI is
selected, an extended bolus (e.g. over 6 hours) may need to be
delivered. FIG. 11(a) shows a bolus-grid which can be suitable for
a patient with a high carbohydrate-to-insulin ratio (CIR) (e.g. 30
g/unit) and with high insulin sensitivity (IS) (e.g. 80
mg/dL/unit).
[0134] FIG. 11(b) illustrates a bolus-grid which can be suitable
for a patient with an average carbohydrate-to-insulin ratio (e.g.
15 g/Unit.) and with average insulin sensitivity (e.g. 40
mg/dL/unit), for example. FIG. 11(c) illustrates a bolus-grid which
can be suitable for a patient with a low carbohydrate-to-insulin
ratio (e.g. 7.5 g/unit) and with low insulin sensitivity (e.g. 20
mg/dL/unit). FIG. 11(d) illustrates a bolus grid which can be
suitable for a patient with an average carbohydrate-to-insulin
ratio (e.g. 15 g/unit.), an average insulin sensitivity (e.g. 40
mg/dL/unit), and with slow gastric emptying (e.g. diabetes induced
gastroparesis).
[0135] With continuous reference to FIG. 7, FIGS. 12-15 illustrate
various embodiments of configuration of the interface (2040)
displayed by the bolus selector (2000). FIG. 12 illustrates one
example of a user interface for the bolus selector (2000) having
navigation windows for the data input. 12a illustrates an example
of a window for setting the carbohydrate-to-insulin ratio (CIR),
insulin sensitivity (IS), and target blood glucose (TBG)
parameters. According to some embodiments, the user can also set
the rules for obtaining the IS value and the CIR. 12b provides an
example of a window for setting current blood glucose levels,
carbohydrate load of the intake, and GI of the intake parameters.
If a meal comprises more than one GI (for example a pizza and a
cake for dessert), a "combined GI" can also be selected. The bolus
selector may comprise delivery patterns suitable for meals
containing combined glycemic indexes, for example, high GI+Low GI
or high GI+intermediate GI.
[0136] The user may enter into a database associated with various
food via the window depicted in 12b by pressing the "Food Data"
soft key (122). 12c illustrates an example of a window, displaying
a recommended selected bolus (bolus dose and delivery pattern). 12d
illustrates an example of a main window of the bolus selector
(2000) through which the user can select any of the windows
presented in 12a-c. Additional windows can be accessible via the
main window (e.g. a window for downloading recent bolus data). 12e
illustrates an example of a window, displaying a database with the
carb load and GI associated with different foods and beverages.
[0137] FIGS. 13a-b show an embodiment of the user interface for the
bolus selector (2000) in which the user can enter his/her BG value
(FIG. 13a). In this embodiment merely a 2 dimensional slice of the
3D bolus grid that corresponds to the entered BG range is displayed
(FIG. 13b). In some embodiments, the user can select the required
bolus by scrolling the buttons (60,60',61,61') and navigating
between different numerical ranges. These ranges quantitatively
represent the carb load of the intake and the GI of the intake,
accordingly. The recommended bolus dose and delivery pattern can be
indicated, as shown by numeral 64. The possible bolus delivery
pattern in the example is one of the following: immediate bolus
(IB), extended bolus (EB) over 1, 4, or 7 hours. Blood glucose
value input (63) (e.g. BG=122) can be ascribed by the bolus
selector (2000) to the relevant range of BG values (e.g.
100<BG<150).
[0138] FIG. 14 illustrates another embodiment of the user interface
for the bolus selector (2000) in which a 2 dimensional slice of the
3D bolus grid that corresponds to the relevant BG range is
displayed. In such an embodiment, the user can select the required
bolus by scrolling the buttons (61, 61', 60, 60') and navigating
between different options qualitatively (for example). For example,
the options can represent the GI of the intake and the carb load of
the intake. The blood glucose value input (63) (e.g. BG=122), as
shown in FIG. 13a, can be ascribed by the bolus selector (2000) to
the relevant range of BG values (e.g. "Intermediate BG").
[0139] FIG. 15 illustrates another embodiment of the user interface
for the bolus selector (2000) in which a 2 dimensional slice of the
3D bolus grid that corresponds to the relevant BG range is
displayed. According to this implementation, the user can select
the required bolus by scrolling the buttons (61',61,60,60') and
navigating between different options (83', 83) represented
graphically as an animation associated with the GI of the intake
and the carb load of the intake. In one variation, the blood
glucose value input (63) (e.g. BG=122), as shown in FIG. 13a, can
be ascribed by the bolus selector (2000) to the relevant range of
BG values (.revreaction.BG). Young children and illiterate users
can especially benefit from the graphical user interface
illustrated in FIG. 15.
[0140] FIGS. 16a-16c show three different embodiments of the
device, each containing a glucometer (90) to be used for measuring
and inputting the blood glucose (BG) inputs for the bolus selector
(2000). FIG. 16a illustrates a glucometer (90) located in the
remote control unit (1008) of the drug delivery device. The
glucometer (90) comprises an opening (95) for receiving of a test
strip (99). A user can extract blood from the body, place the blood
on the test strip (99) and inserts the strip into the opening (95).
The glucose readings can be displayed on the screen (80) of the
remote control unit (1008).
[0141] FIG. 16b illustrates a glucometer (90) located in the
reusable part (1) of the dispensing patch unit (1010). A
communication channel (300) between the glucometer (90) residing in
the dispensing patch unit (1010) and the bolus selector (2000)
residing in the remote control unit (1008) is maintained, allowing
programming, data handling, and user inputs. FIG. 16c illustrates
an embodiment in which glucose readings can be received from a
separate independent glucometer (90).
[0142] FIGS. 17a-b show another embodiment of the disclosure in
which blood glucose readings can be manually loaded to the bolus
selector (2000), or automatically received by the bolus selector
(2000), from a continuous subcutaneous glucose monitor (1006). A
communication channel between the continuous subcutaneous glucose
monitor (1006) and the bolus selector (2000) residing in the remote
control unit (1008) can be maintained, allowing programming, data
handling, and user inputs.
[0143] FIG. 17a illustrates an embodiment in which the current
blood glucose concentration is received from an independent
continuous subcutaneous glucose monitor (1006) and loaded by the
patient to the bolus selector (2000). FIG. 17b illustrates an
embodiment in which the continuous subcutaneous glucose sensing
apparatus (1006) is located in the dispensing patch unit (1010) of
the insulin delivery device.
[0144] As disclosed in our previous PCT application
PCT/IL07/000163, herein incorporated by reference in its entirety,
the insulin dispensing apparatus (1005) and glucose sensing
apparatus (1006) constitute, in the illustrated embodiment, a
single insulin delivery device, and may share a single cannula (6)
for both dispensing and sensing functions. Alternatively, the
sensing apparatus and the dispensing apparatus may have separate
cannulae that penetrate the skin (5) and reside in the subcutaneous
tissue.
[0145] In another embodiment, the device can be configured to
operate as a semi-closed loop system. In a semi-closed system, the
feedback and control between sensor measurements and therapeutic
fluid release can be partially automatic. For example, the release
of the therapeutic fluid in a basal rate can be automatically
controlled by the processor based on various measurements of
analytes, while the release of bolus doses of the therapeutic fluid
can still be delivered based on according to the user's input.
Insulin can automatically be dispensed according to continuous
monitoring of glucose levels and according to additional user
inputs (semi-closed loop). For example, the bolus selector (2000)
can be used for bolus inputs in the semi-closed loop system.
[0146] FIG. 18 illustrates the bolus selector data inputs that can
be used for patient specific bolus-grid retrieval by the bolus
selector (2000). The carbs load of the intake and GI of the intake
can be manually configured. The current blood glucose levels can
also be manually configured. For example, the user can check his
blood glucose level with the aid of a glucometer, a continuous
subcutaneous glucose monitoring device, or any other suitable means
known in the art for measuring blood glucose levels.
[0147] Alternatively, the current blood glucose levels can be
configured automatically. For example, the device can comprise a
glucometer and a communication channel between the bolus selector
and the glucometer, to allow direct input of the measured blood
glucose levels. In another embodiment, a communication channel can
exit between the bolus selector and an independent glucometer, to
allow direct input of the measured blood glucose levels.
[0148] In another embodiment, a continuous subcutaneous glucose
monitoring apparatus can continuously transmit BG levels to the
bolus selector. According to another embodiment, a communication
channel can exist between the bolus selector and an independent
continuous subcutaneous glucose monitoring device, allowing direct
transmission of the measured blood glucose.
[0149] The data concerning the residual insulin (time and dose of
last bolus) can be obtained manually or automatically, allowing
subtraction of the appropriate amount from the selected bolus dose.
The carbohydrate-to-insulin ratio (CIR), insulin sensitivity (IS),
and target blood glucose (TBG) can be used by the bolus selector
according to the initial settings of the user. In some embodiments,
the CIR, IS and TBG values can be adjusted manually.
[0150] FIG. 19 illustrates another embodiment of the device, where
the bolus selector (2000), is located in a remote control unit
(1008) and communicates with an external PC (80). In some
embodiments, the 3D bolus-grids that correspond to the user's
particular preset IS value, CIR, and TBG may be saved in the memory
of the bolus selector (2000) in the remote control (1008) while the
rest of the bolus-grids (i.e. bolus-grids that correspond to other
IS values, CIR Ratios, or TBG values) can be saved in the memory of
the external PC (80). If the diabetic state of the user changes,
the bolus-grids that correspond to, the new IS and/or CIR and/or
TBG can be downloaded from the external PC (80) to the bolus
selector memory in addition to, or instead of, the previous stored
3D bolus-grids.
[0151] According to some embodiments, the delivery patterns of the
bolus-grids can be tailored to a specific user. Different users may
require different delivery patterns for the same GI. For example, a
user with gastroparesis may require delivery patterns over longer
periods of time to accommodate for the slow gastric emptying. On
the other hand, users who suffer from dumping syndrome may need
delivery patterns over shorter periods of time to accommodate for
the rapid gastric emptying.
[0152] The tailoring of the bolus-grids, prior to the system use,
can be carried out directly via the remote control unit (1008), for
example. The bolus-grids can also be pre-determined with the aim of
a PC (80) and downloaded afterwards to the bolus selector (2000)
residing in the remote control unit (1008).
[0153] FIG. 20a illustrates an example of a 2 dimensional slice of
the 3D bolus grid, corresponding to an intake with a high GI. In
this case, an immediate bolus can be recommended. The bolus-grid in
the example can be suitable for a user with an IS value of 40
mg/dL/unit, an IS/CIR ratio of 3 (i.e. CIR=13.3 g/unit), and a
target BG level of 100 mg/dL. As shown, each range (either of blood
glucose (BG) levels or carbs) has a low boundary and a high
boundary defining the range, for example. Each range is represented
by a discrete value designated as a reference value ("Ref.") which
is applied in the calculations of the pre-determined bolus.
[0154] In some embodiments, the reference value is not necessarily
the mid-range value but rather a value closer to the lower portion
of each range. In some embodiments, the reference value may be
intentionally shifted during generation of the pre-determined
bolus-grids, for example, higher than the mid-range value. In some
examples, the reference value may be equal to the upper boundary
value (e.g. in a range of 20 to 40, the reference value may be 40).
The rationale for this shift is that it may minimize human error in
estimating the carb load to be ingested. This error can be
frequently caused by the tendency of users to underestimate the
amount of carbohydrates.
[0155] In some embodiments, during generation of the pre-determined
bolus-grids, each cell value of a bolus-grid (presented in units of
insulin) can be selected to lead the BG concentrations to fall
within a pre-defined allowable clinical range of blood glucose
levels, for example. This clinical range can be bounded between two
discrete values of blood glucose levels: a lower boundary
referred-to as the "minimal undershoot", and an upper boundary
referred-to as the "maximal overshoot". The minimal undershoot and
the maximal overshoot can be, for example, 60 mg/dL and 200 mg/dL,
respectively. If an insulin value within a cell causes the blood
glucose level of the patient to be outside of the allowable range,
(i.e. <60 mg/dL or >200 mg/dL), the patient can likely suffer
from hypoglycemia or hyperglycemia, which may be hazardous.
[0156] According to some embodiments, the selection of a value of
insulin bolus dose for a particular cell can be done using a
verification process that tests the boundary values of the blood
glucose range and the carbohydrate intake range corresponding to
that cell.
[0157] For example, the cell value which corresponds to the blood
glucose (BG) range 130 mg/dL to 160 mg/dL, and carbohydrate intake
range of 40 grams to 60 grams can first be calculated according to
the reference values, i.e. BG of 145 mg/dL and carbohydrate intake
of 45 grams yielding the value of 4.5 units of insulin to be
administered. The verification process can calculate a lower value
based on the low boundary of the BG and carbohydrate intake ranges
(i.e. BG=130 mg/dL and carbs=40 grams), and an upper value based on
the high boundary of the ranges (i.e. BG=160 mg/dL and carbs=60
grams), resulting in a lower value of 3.76 Units and the upper
value of 6 Units. The absolute difference between the lower value
(3.76 Units) and the cell value (4.5 Units) equals to 0.74 Units,
and is referred-to as "low_diff". The low_diff difference can bring
the BG level of the patient to approximately 70 mg/dL. For example,
this can be calculated by using the following formula:
TBG-low_diff*IS. Following the example presented above, the
low_diff value can bring the BG level of the patient to
100-0.74*40=70.4 mg/dL.
[0158] A similar procedure can be done with the upper value: the
absolute difference between the upper value (6 Units) and the cell
value (4.5 Units) is determined to be 1.5 Units, and referred-to as
"upper_diff" (for example). This difference could bring the BG
level of the patient to a value of approximately 160 mg/dL. If one
of the values (70 mg/dL or 160 mg/dL) falls outside of the clinical
range defined by the minimal undershoot and the maximal overshot,
then, in some embodiments, the reference value and/or values of the
BG and carbohydrate intake ranges can be re-assessed.
[0159] The verification procedure described above can be carried
out iteratively to determine the optimal cell value ensuring that
the BG level of the patient remains in the allowed clinical range.
In some embodiments, a single clinical range (i.e. minimal
undershoot and maximal overshoot) can be defined for all the cells
of the bolus-grid. In some embodiments, a different clinical range
can be defined for each cell of the bolus-grid. In some
embodiments, the patient/user can define/program parameters such as
minimal undershoot, maximal overshoot and/or boundaries of the
ranges, adjusting the bolus-grid to be tailored to his/her own
individual needs. In some embodiments, the BG levels corresponding
to "low_diff" and "upper_diff" values can be pre-calculated and
stored in a database table. For example, FIGS. 20b and 20c show the
corresponding minimal undershoot and maximal overshoot tables,
respectively. Specifically, the table 20b provides a list of
minimal undershoot values for each of the BG ranges and for each of
the six carbohydrate intake ranges presented in FIG. 20a. In some
embodiments, the tables 18b and 18c are not presented to the
user.
[0160] For example, according to the table 20b, the minimal
allowable undershoot value is 70 mg/dL. According to table 20c, the
maximum allowable overshoot value is 160 mg/dL. In some
embodiments, the undershoot and/or overshoot values, lower and/or
upper boundaries of the ranges and other bolus-grid parameters can
be adjusted.
[0161] FIGS. 21a-f illustrate graphic representations of exemplary
pre-determined bolus delivery patterns which can be recommended to
the user by the bolus selector. For example, FIG. 21a depicts a
delivery pattern in which the entire bolus dose is delivered as
rapidly as possible. This pattern can be suitable for a meal that
is rapidly absorbed from the gut, i.e., a meal that is attributed
as having a high glycemic index. An example of such meal is
cornflakes or fruit.
[0162] FIG. 21b depicts a delivery pattern in which the bolus dose
is delivered evenly over a period of 1 hour. This may be suitable
for a meal that is relatively slowly absorbed from the gut, i.e., a
meal of a low glycemic index or high in fat, such as pizza. FIG.
21c depicts a delivery pattern in which the bolus dose is delivered
evenly over a period of 4 hours. This may be suitable for a meal
that is very slowly absorbed from the gut, i.e., a meal of a very
low glycemic index or very high in fat, such as steak.
[0163] FIG. 21d depicts a delivery pattern in which a portion of
the bolus dose is delivered immediately and the remaining dose is
delivered evenly over a prolonged period of time. In the depicted
pattern, the immediate portion comprises 60% of the total dose, and
the remaining 40%. The remaining portion is delivered over the
period of 2 hours. For example, such a delivery pattern can be
suitable for a meal that comprises both rapidly (high GI) and
slowly (intermediate GI) absorbed carbohydrates, such as fruit and
pasta.
[0164] The pattern depicted on FIG. 21d can also be suitable when
the elevated blood glucose value needs to be corrected before a
meal corresponding to an intermediate glycemic index. The insulin
needed for correction of the BG can be accounted for in the
immediate portion of the bolus and the slowly absorbed meal can be
accounted for in the proceeding, relatively long, time interval.
For example, if a user is planning to eat a meal corresponding to
an intermediate GI and the user's current BG is high, then the
following two boluses can be used: [0165] an immediate correction
bolus delivered to bring the high BG level to a target value; and
[0166] an extended bolus delivered over a period of time to balance
the meal with an intermediate GI.
[0167] FIG. 21e depicts another delivery pattern in which a portion
of the bolus dose is delivered immediately and the remaining dose
is delivered evenly over a prolonged period of time. In the
depicted pattern, the immediate portion comprises 60% of the total
dose, and the remaining 40% are delivered over the following 4
hours. Such a delivery pattern may be suitable for a meal that
comprises both rapidly (high GI) and very slowly (low GI) absorbed
carbohydrates, such as fruit and pork ribs. Such a pattern is also
suitable when correction of elevated blood glucose value is needed
before a meal having low glycemic index.
[0168] Various embodiments of the subject matter described herein
can be realized in digital electronic circuitry, integrated
circuitry, specially designed ASICs (application specific
integrated circuits), computer hardware, firmware, software, and/or
combinations thereof. These various embodiments may include
implementation in one or more computer programs that are executable
and/or interpretable on a programmable system including at least
one programmable processor, which can be special or general
purpose, coupled to receive data and instructions from, and to
transmit data and instructions to, a storage system, at least one
input device, and at least one output device.
[0169] These computer programs (also known as programs, software,
software applications or code) include machine instructions for a
programmable processor, and can be implemented in a high-level
procedural and/or object-oriented programming language, and/or in
assembly/machine language. As used herein, the term
"machine-readable medium" refers to any computer program product,
apparatus and/or device (e.g., magnetic discs, optical disks,
memory, Programmable Logic Devices (PLDs)) used to provide machine
instructions and/or data to a programmable processor, including a
machine-readable medium that receives machine instructions as a
machine-readable signal. The term "machine-readable signal" refers
to any signal used to provide machine instructions and/or data to a
programmable processor.
[0170] To provide for interaction with a user, the subject matter
described herein can be implemented on a computer having a display
device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal
display) monitor, or other display device) for displaying
information to the user and a keyboard and a pointing device (e.g.,
a mouse or a trackball) by which the user may provide input to the
computer. Other kinds of devices can be used to provide for
interaction with a user as well; for example, feedback provided to
the user can be any form of sensory feedback (e.g., visual
feedback, auditory feedback, or tactile feedback); and input from
the user can be received in any form, including acoustic, speech,
or tactile input.
[0171] The subject matter described herein can be implemented in a
computing system that includes a back-end component (e.g., as a
data server), or that includes a middleware component (e.g., an
application server), or that includes a front-end component (e.g.,
a client computer having a graphical user interface or a Web
browser through which a user may interact with an implementation of
the subject matter described herein), or any combination of such
back-end, middleware, or front-end components. The components of
the system can be interconnected by any form or medium of digital
data communication (e.g., a communication network). Examples of
communication networks include a local area network ("LAN"), a wide
area network ("WAN"), and the Internet.
[0172] The computing system may include clients and servers. A
client and server are generally remote from each other and
typically interact through a communication network. The
relationship of client and server arises by virtue of computer
programs running on the respective computers and having a
client-server relationship to each other.
[0173] Some embodiments of the present disclosure preferably
implement the bolus selection feature via software operated on a
processor contained in a remote control device of an insulin
dispensing system and/or a processor contained in a insulin
dispensing device being party of an insulin dispensing system.
[0174] Any and all references to publications or other documents,
including but not limited to, patents, patent applications,
articles, webpages, books, etc., presented in the present
application, are herein incorporated by reference in their
entirety.
[0175] Although a few variations have been described in detail
above, other modifications are possible. For example, the logic
flow depicted in the accompanying figures and described herein does
not require the particular order shown, or sequential order, to
achieve desirable results. Other embodiments can be within the
scope of the following claims.
* * * * *